Hypertonicity of extracellular fluid and hypovolemia are reliable stimuli of water drinking, but whether animals eating and drinking freely ever experience these classic stimuli to thirst is questionable. Under ad libitum conditions most water drunk is taken in close association with meals and anticipates the osmotic load that the meal represents. The long term aim is to find out what water intake control mechanisms operate in freely eating and drinking animals. Knowledge of such controls, and their relation to food intake, is important in understanding many diseases where there are disturbances of water or food intake, or of fluid balance. Specific aims and methods: 1. To determine whether the classic thirst stimuli are the causes of meal-associated drinking. Blood samples will be taken from undisturbed pigs upon initiation of drinking and for comparison at times of nondrinking. Osmolality will be measured and blood volume changes estimated from packed cell volume and plasma protein concentration data. Changes in blood volume will also be assessed with dilution techniques utilizing long-persisting agents as Evans Blue. The control pathway from hypovolemia to increased drinking may include stimulation of pressoreceptors in arteries, large veins and right and left atria. Miniature pressure transducers will be used to measure such changes at these sites when spontaneous drinking occurs. Release of renin by hypovolemia (or sympathetic excitation) and the formation of angiotensin II will be studied using blocking agents. 2. Agents that cause gastric secretion cause water drinking, suggesting that gastric secretion could be a cause of meal-associated drinking. a.) If gastric juice is a stimulus to sensory receptors in the gastric mucosa, drinking should be elicited by intragastric infusion of acid or gastric juice, or blocked by topical anesthesia of the mucosa or selective vagotomy of the stomach. b.) Gastric secretion will also cause a slight fall in blood volume, which could result in a significant fall of pressure within the great veins and atria, but with no fall in arterial pressure. Pressure measurements during gastric secretion should indicate whether this occurs.